Opinion|Videos|September 10, 2026

Toxicity Management of PI3K Pathway Inhibitors in HR+/HER2− mBC

Author(s)Seth Wander, MD, PhD, Erica L. Mayer, MD, MPH, Kathryn Post, PhD, RN, ANP-BC

Clinicians weigh alpelisib’s hyperglycemia, rash, diarrhea and increasingly favor capivasertib for lower glucose risk with close monitoring.

Episodes in this series

EP. 1 Second-Line Treatment Considerations in HR+/HER2− mBC

EP. 1 Second-Line Treatment Considerations in HR+/HER2− mBC

EP. 2 Biomarker Testing and Treatment Selection in HR+/HER2− mBC

EP. 2 Biomarker Testing and Treatment Selection in HR+/HER2− mBC

EP. 3 Treatment Strategies for Biomarker-Negative and PI3K-Pathway Altered HR+/HER2− mBC

EP. 3 Treatment Strategies for Biomarker-Negative and PI3K-Pathway Altered HR+/HER2− mBC

EP. 4 Toxicity Management of PI3K Pathway Inhibitors in HR+/HER2− mBC

EP. 4 Toxicity Management of PI3K Pathway Inhibitors in HR+/HER2− mBC

The panel examines the toxicity profiles and practical considerations associated with PI3K pathway-directed therapies in hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2− mBC). Dr. Jennifer Hutchinson reviews experience with alpelisib plus fulvestrant, highlighting hyperglycemia as a major treatment-limiting toxicity and emphasizing the importance of assessing baseline metabolic risk, including diabetes history and hemoglobin A1C, before treatment. The panel discusses proactive glucose monitoring, home glucose checks, potential use of metformin, treatment interruption or dose modification, and management of diarrhea and rash with supportive measures. Dr. Hutchinson then compares alpelisib with capivasertib, noting the lower incidence of hyperglycemia observed with capivasertib, alongside greater rates of diarrhea and rash that may occur early after treatment initiation. Dr. Post describes how these toxicity considerations have influenced practice, with greater use of capivasertib-based therapy compared with alpelisib. The discussion also reinforces the importance of comprehensive genomic testing throughout the treatment journey to help identify appropriate targeted options for patients with HR+/HER2− mBC.

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